60 years of metformin use: a glance at the past and a look to the future

To mark the 60th anniversary of the first clinical use of metformin for diabetes, Diabetologia has commissioned a series of articles on the many evolving (and controversial) aspects of metformin use. To begin, a historical overview is provided by Clifford Bailey, followed by an outline of the mechanisms of action by Rena et al. Sanchez-Rangel and Inzucchi go on to present data for the efficacy and safety of metformin in type 2 diabetes, for which it is the first-line therapy. In contrast, Livingstone and colleagues discuss its use in type 1 diabetes and Aroda et al present findings for its potential use for diabetes prevention. Griffin et al investigate the association between metformin and cardiovascular disease risk by conducting a meta-analysis, whilst Sam and Ehrmann and Lindsay and Loeken discuss its use in polycystic ovary syndrome and pregnancy, respectively. Metformin therapy in the ageing population is reviewed by Valencia et al, and Michael Pollak confers the non-glycaemic effects of metformin, suggesting a role for the human microbiota/gut metabolome and the immune system. Another emerging area of interest, the impact of metformin on cancer incidence and mortality, is covered by Heckman-Stoddard et al. Finally, to address the heterogeneity in response to metformin therapy, Jose Florez advises how a personalised approach may be achieved using genetic studies. In summary, this review series demonstrates how metformin shows promise in many conditions, but how long can this drug remain at the top spot?
This review set is accompanied by an editorial by Sally Marshall: 60 years of metformin use: what we have learnt and what we have yet to discover

Metformin: historical overview
Clifford J. Bailey
The mechanisms of action of metformin
Graham Rena, D. Grahame Hardie, Ewan R. Pearson
Metformin: clinical use in type 2 diabetes
Elizabeth Sanchez-Rangel, Silvio E. Inzucchi
A new perspective on metformin therapy in type 1 diabetes
Rachel Livingstone, James G. Boyle, John R. Petrie, on behalf of The REMOVAL Study Team
Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study
Vanita R. Aroda, William C. Knowler, Jill P. Crandall, Leigh Perreault, Sharon L. Edelstein, Susan L. Jeffries, Mark E. Molitch, Xavier Pi-Sunyer, Christine Darwin, Brandy M. Heckman-Stoddard, Marinella Temprosa, Steven E. Kahn, David M. Nathan, for the Diabetes Prevention Program Research Group
Metformin use in pregnancy: promises and uncertainties
Robert S. Lindsay, Mary R. Loeken
Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes
Simon J. Griffin, James K. Leaver, Greg J. Irving
Metformin and ageing: improving ageing outcomes beyond glycaemic control
Willy Marcos Valencia, Ana Palacio, Leonardo Tamariz, Hermes Florez
Repurposing metformin for the prevention of cancer and cancer recurrence
Brandy M. Heckman-Stoddard, Andrea DeCensi, Vikrant V. Sahasrabuddhe, Leslie G. Ford
The pharmacogenetics of metformin
Jose C. Florez
Metformin therapy for the reproductive and metabolic consequences of polycystic ovary syndrome
Susan Sam, David A. Ehrmann